Baicalin has anti-inflammatory, antibacterial, blood platelet aggregation-inhibiting, free oxygen radical-clearing, and endotoxin-decreasing properties. However, its molecular mechanism involved in the treatment of Adriamycin-induced nephrotic syndrome (NS) is still unclear.This study aimed to explore the effects of baicalin on Adriamycin-induced nephrotic syndrome (NS) and to characterize the genes involved in this progression.We established Adriamycin-induced NS model in 32 rats and used six rats in Sham group. Urinary total protein content and creatinine serum were assessed as physiological indicators. H&E staining was used to observe the pathological changes. We determined gene expression profiles using transcriptome sequencing in the rat kidney tissues from Sham, Adriamycin, and Adriamycin + baicalin groups. KEGG was carried out to analyze the enriched pathways of differentially expressed genes among these groups.Baicalin treatment relieved renal injury in NS rats. Expression of 363 genes was significantly different between the Adriamycin and Adriamycin + baicalin M groups. Most of the differentially expressed genes were enriched in pathways involved in epithelial-mesenchymal transition (EMT), fibrosis, apoptosis, and inflammation.Overall, these data suggest that Adriamycin-induced NS can be attenuated by baicalin through the suppression of fibrosis-related genes and inflammatory reactions. Baicalin is a potential drug candidate for the treatment of NS, and the identified genes represent potential therapeutic targets.